Involvement of Cyr61 in growth, migration, and metastasis of prostate cancer cells.
Cyr61 has been reported to participate in the development and progression of various cancers; however, its role in prostate cancer (PCa) still remains poorly understood. In this study, we explored the function of Cyr61 in a series of malignant PCa cell lines, including LnCap, Du145, and PC3. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet assays demonstrated that Cyr61 was essential for the proliferation of PCa cells. Soft agar assay and xenograft analysis showed that downregulation of Cyr61 suppressed the tumorigenicity of Du145 cells both in vitro and in vivo. Either silencing the cellular Cyr61 by RNA interference or neutralising the endogenous Cyr61 by antibody inhibited the migration of Du145 cells. In contrast, purified protein of Cyr61 promoted the migration of LnCap cells in a dose-dependent manner. These results suggested that Cyr61 was involved in the migration of PCa cells. We also observed the accumulation of mature focal adhesion complexes associated with the impaired migration through Cyr61 downregulation. Also, further studies showed that Cyr61 regulated the level of activated Rac1 as well as its downstream targets, including phosphorylated JNK, E-cadherin, and p27(kip1), which are key molecules involved in cell growth, migration, and invasion. The in vivo mouse tail vein injection experiment revealed that Cyr61 affected the metastatic capacity of Du145 cells, suggesting that Cyr61 was required for prostate tumour metastasis. Altogether, our results demonstrated that Cyr61 played an important role in the tumorigenicity and metastasis of PCa cells, which will benefit the development of therapeutic strategy for PCas.
Sun
Z-J
ZJ
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Wang
Y
Y
Cai
Z
Z
Chen
P-P
PP
Tong
X-J
XJ
Xie
D
D
D049108:Cell Enlargement; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D055515:Cysteine-Rich Protein 61 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*
C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61